Fourier love all around as Repatha improves outcomes

Amgen’s worst-case scenario from the outcomes trial of Repatha can be dismissed. The California-based group says the cholesterol-lowering jab reduced risk of heart attacks, strokes and cardiovascular events, raising the odds that insurers will extend coverage to more than just patients with established atherosclerotic disease.

When detailed data are disclosed at a medical meeting next month, payers will watch closely for signs that Repatha can avert downstream healthcare costs to justify its $1,000-a-month pricetag. Meanwhile, rivals Sanofi and Regeneron have seen the evaporation of one legal argument in favour of keeping the competing Praluent on the US market as a potential withdrawal date nears in the companies’ patent infringement litigation.

More eligible patients

The Fourier trial in 27,500 patients aimed to widen use of Repatha, a PCSK9-blocking antibody, to heart disease patients at high risk of suffering myocardial infarction or other cardiovascular events. The drug currently has a US label allowing use in patients with familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease.

In Fourier it was used in addition to statin therapy in patients with elevated LDL cholesterol. The trial ended when 1,630 events had been recorded, which investigators said should provide 90% power to detect a relative reduction of 15% or more in the secondary endpoint, which was a composite of cardiovascular death, myocardial infarction, or stroke – thus it is safe to assume that the 15% standard was met or exceeded.

By how much will be the question that Amgen will reveal at the American College of Cardiology meeting in Washington on March 17, and the answer will be watched closely not only by specialists but also by payers, who will be doing their own calculations on the downstream benefits of Repatha use.

Meta-analyses of data from statin trials have concluded that for every 39mg/dl of LDL lowering, the risk of cardiovascular events is cut by 21%. In the pivotal trial that supported US FDA approval for atherosclerotic patients, Repatha plus statins lowered LDL by 64% from a baseline of 108mg/dl, or by about 69mg/dl, although the Fourier trial enrolees had a slightly lower baseline mean LDL of 91.5mg/dl.

Nevertheless, high expectations have been based around the potent LDL-reducing capacities of Repatha and other PCSK9s. Assuming the 15% reduction in the secondary endpoint – the “hard” major adverse cardiovascular event (MACE) measure in which regulators and specialists will be most interested – Amgen should be able to add an outcomes benefit to the label.

Amgen shares were up 5% in early trading today.

Economics

The primary endpoint will be of more interest to payers, however, because this includes not just MACE but also hospitalisations for unstable angina or coronary revascularisation. The measurement of additional events will give insurers and pharmacy benefit managers a wider view of how downstream healthcare costs can be averted through use of Repatha.

Amgen aims to begin discussing economic benefits with payers even before the FDA has weighed in, thanks to agency guidance published last month.

“We can clearly go out and talk about the topline data and talk conceptually with payers about the value this data brings to them,” Anthony Hooper, Amgen’s executive vice-president for global commercial operations, said in the group’s fourth-quarter earnings call. “We can’t, however, at this particular stage, promote it from a sales perspective because it's not into the label yet, but we can talk to payers.”

He added that payer restrictions had kept Repatha from patients eligible for treatment based on the label – a statement confirmed by the substantial downgrades in sales forecasts that have occurred in the past year.

Legally speaking

The Fourier findings also increase the chances that competitor Praluent will be withdrawn from the US market. Amgen won a permanent injunction against Sanofi and Regeneron for marketing Praluent while infringing Repatha’s patents, although there is a temporary stay on Praluent’s exclusion that expires later this month (Amgen in position to dictate terms in PCSK9 tussle, January 6, 2017).

One of Sanofi and Regeneron’s arguments against exclusion has been that the public is better served if it has treatment options. Had Fourier failed to show a benefit while the Odyssey Outcomes trial of Praluent was still awaiting results, the Sanofi and Regeneron “public good” argument would have been strengthened.

Instead, Praluent’s sponsors will go into upcoming court dates with a weakened case at a time when Amgen is looking forward to taking a stronger economic case to payers.